Mechanism of Ranitidine Associated Anemia

• Published in: The American journal of the medical sciences 1989-06, Vol.297 (6), p.369-371
• Main Authors: Pixley, John S., Mackintosh, F. Roy, Sahr, Elizabeth A., Zanjani, Esmail D.
• Format: Article
• Language: English
• Subjects: Anemia - blood; Anemia - chemically induced; Anemia - immunology; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow - pathology; Coombs Test; Coombs’ Positivity; Drug toxicity and drugs side effects treatment; Drug-Induced Anemia; Erythrocytes - drug effects; Erythrocytes - immunology; Hematopoietic Progenitors; Hematopoietic Stem Cells - drug effects; Histamine - pharmacology; Histamine Receptor; Humans; In Vitro Techniques; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Ranitidine; Ranitidine - adverse effects; Ranitidine - antagonists & inhibitors; Thrombocytopenia - chemically induced; Toxicity: blood
• ISSN: 0002-9629; 1538-2990
• DOI: 10.1097/00000441-198906000-00007

Ranitidine, an H2 receptor antagonist, has been associated with hematotoxicity. The mechanism(s) underlying this toxicity is not well understood. The authors studied the mechanism of anemia in a patient with ranitidine associated anemia and thrombocytopenia. Clinical evaluation suggested drug-induced Coombs’ positive reticulocytopenic hemolysis. In vitro, with the patient off ranitidine, the authors were able to induce Coombs’ positivity by incubating patient’s red cells with ranitidine and his serum. This process was inhibited by prior exposure of his red cells to histamine. In vitro studies using clonal assays for hematopoietic progenitors revealed that while the patient’s serum or ranitidine alone did not affect the patient’s or normal bone marrow hematopoiesis, the simultaneous presence of both agents significantly suppressed both patient’s and normal erythroid progenitor (BFU-E) colony development. This suppressive effect was prevented by the prior exposure of marrow to histamine and was not observed when the patient’s serum was heat inactivated. These studies suggest that the anemia may have resulted from complement-dependent autoimmune destruction/inhibition of progenitor/mature erythroid cells by a process critically dependent on the presence of ranitidine and possibly acting at or near the histamine receptor.